Intercellular communication between smooth muscle ceils depends on diffusion of signals through gap junction channels as well as release of substances to which receptors in adjacent cells respond. One major class of pharmacological receptors is the purinergic P2 receptors that respond to purine and pyrimidine nucleotides and nucleosides with an increase in intracellular Ca2+. One goal of this Project is to identify functionally active P2 receptor subtypes and gap junction proteins in bladder and corporal smooth muscles and to determine the roles that these receptors and channels play in the propagation of intercellular Ca2+ waves. Development of diabetes in streptozotocin-treated and BBAN rats is characterized by loss of innervation in smooth muscle targets. Thus, another major goal of these studies is to determine whether intercellular Ca2+ signaling changes and whether changes in the expression and function of gap junctions and P2 receptors underlie these alterations.